Lefkou Eleftheria, Mamopoulos Apostolos, Dagklis Themistoklis, Vosnakis Christos, Rousso David, Girardi Guillermina
J Clin Invest. 2016 Aug 1;126(8):2933-40. doi: 10.1172/JCI86957. Epub 2016 Jul 25.
Administration of conventional antithrombotic treatment (low-dose aspirin plus low-molecular weight heparin [LDA+LMWH]) for obstetric antiphospholipid syndrome (APS) does not prevent life-threatening placenta insufficiency-associated complications such as preeclampsia (PE) and intrauterine growth restriction (IUGR) in 20% of patients. Statins have been linked to improved pregnancy outcomes in mouse models of PE and APS, possibly due to their protective effects on endothelium. Here, we investigated the use of pravastatin in LDA+LMWH-refractory APS in patients at an increased risk of adverse pregnancy outcomes.
We studied 21 pregnant women with APS who developed PE and/or IUGR during treatment with LDA+LMWH. A control group of 10 patients received only LDA+LMWH. Eleven patients received pravastatin (20 mg/d) in addition to LDA+LMWH at the onset of PE and/or IUGR. Uteroplacental blood hemodynamics, progression of PE features (hypertension and proteinuria), and fetal/neonatal outcomes were evaluated.
In the control group, all deliveries occurred preterm and only 6 of 11 neonates survived. Of the 6 surviving neonates, 3 showed abnormal development. Patients who received both pravastatin and LDA+LMWH exhibited increased placental blood flow and improvements in PE features. These beneficial effects were observed as early as 10 days after pravastatin treatment onset. Pravastatin treatment combined with LDA+LMWH was also associated with live births that occurred close to full term in all patients.
The present study suggests that pravastatin may improve pregnancy outcomes in women with refractory obstetric APS when taken at the onset of PE or IUGR until the end of pregnancy.
对于产科抗磷脂综合征(APS),采用传统抗血栓治疗(小剂量阿司匹林加低分子肝素[LDA+LMWH])并不能预防20%的患者发生危及生命的胎盘功能不全相关并发症,如子痫前期(PE)和胎儿生长受限(IUGR)。他汀类药物已被证明可改善PE和APS小鼠模型的妊娠结局,这可能与其对内皮的保护作用有关。在此,我们研究了普伐他汀在LDA+LMWH治疗无效且妊娠不良结局风险增加的APS患者中的应用。
我们研究了21例在LDA+LMWH治疗期间发生PE和/或IUGR的APS孕妇。10例患者组成的对照组仅接受LDA+LMWH治疗。11例患者在发生PE和/或IUGR时,除接受LDA+LMWH治疗外,还接受普伐他汀(20mg/d)治疗。评估子宫胎盘血流动力学、PE特征(高血压和蛋白尿)的进展以及胎儿/新生儿结局。
对照组所有分娩均为早产,11例新生儿中仅6例存活。在6例存活的新生儿中,3例发育异常。接受普伐他汀和LDA+LMWH联合治疗的患者胎盘血流增加,PE特征有所改善。这些有益效果在普伐他汀治疗开始后10天就已观察到。普伐他汀与LDA+LMWH联合治疗还使所有患者的活产接近足月。
本研究表明,普伐他汀在PE或IUGR发生时开始服用直至妊娠结束,可能改善难治性产科APS女性的妊娠结局。